Reduced-dose chemotherapy and blinatumomab as induction treatment for newly diagnosed Ph-negative B-cell precursor acute lymphoblastic leukemia: a phase 2 trial.

Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.

Osmapentalenofurans Constructed by Reacting Os≡C1 of Osmapentalyne with Phenols.

Over the past decade, significant research efforts have focused on osmapentalyne, characterized by the more reactive Os≡C7 (Carbon atoms numbered in a clockwise direction on the osmapentalyne skeleton), across areas encompassing electrophilic, nucleophilic, and addition reactions. Nevertheless, the reactivity of osmapentalyne featuring Os≡C1 remains ripe for further exploration. In this investigation, we effectively synthesized a lineage of osmapentalenofurans through the nucleophilic reaction of osmapentalyne incorporating Os≡C1 with phenols. These resulting complexes demonstrate near-infrared luminescence traits in both solid and liquid states. Particularly noteworthy is the osmapentalenofuran derived from tetraphenylethane (TPE) unit, which showcases remarkable aggregation-induced emission ( AIE) property in the aggregated state. These osmapentalenofurans are also able to further extend their range of reactions, including reactions with base and isonitrile. This study not only broadens the scope of applications for metal aromatics but also furnishes valuable insights into the realm of specialized functional materials.

An Improved ELOS Guidance Law for Path Following of Underactuated Unmanned Surface Vehicles.

In this paper, targeting the problem that it is difficult to deal with the time-varying sideslip angle of an underactuated unmanned surface vehicle (USV), a line-of-sight (LOS) guidance law based on an improved extended state observer (ESO) is proposed. A reduced-order ESO is introduced into the identification of the sideslip angle caused by the environmental disturbance, which ensures a fast and accurate estimation of the sideslip angle. This enables the USV to follow the reference path with high precision, despite external disturbances from wind, waves, and currents. These unknown disturbances are modeled as drift, which the modified ESO-based LOS guidance law compensates for using the ESO. In the guidance subsystem incorporating the reduced-order state observer, the observer estimation and track errors are proved uniformly ultimately bounded. Simulation and experimental results are presented to validate the effectiveness of the proposed method. The simulation and comparison results demonstrate that the proposed ELOS guidance can help a USV track different types of paths quickly and smoothly. Additionally, the experimental results confirm the feasibility of the method.

Separator engineering: Assisting lithium salt dissociation and constructing LiF-rich solid electrolyte interphases for high-rate lithium metal batteries.

Challenges associated with lithium dendrite growth and the formation of dead lithium significantly limit the achievable energy density of lithium metal batteries (LMBs), particularly under high operating current densities. Our innovative design employs a state-of-the-art 2500 separator featuring a meticulously engineered cellulose acetate (CA) coating (CA@2500) to suppress dendrite nucleation and propagation. The CO functional groups in CA enhances charge transfer kinetics and triggering the decomposition of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), which leads to the formation of a more robust solid electrolyte interphase (SEI) composed primarily of LiF. Moreover, the introduction of polar functional groups in the CA enhances the separator's hydrophilic properties, facilitating the uniform Li+ flux and creating a conductive pathway for efficient lithium migration. As a result, the CA@2500 separator exhibits a high lithium-ion transfer number (0.88) and conductivity. The lithium symmetric cell assembles with the CA@2500 separator displays a stable cycling performance over 5500 h at a current density and capacity of 10 mA cm-2 and 10 mAh cm-2, respectively. Additionally, LPF battery with CA@2500 separator shows an excellent capacity retention at 0.2 C with an average decay of 0.055 % per cycle. Moreover, a high capacity of 105 mAh g-1 is maintained after 500 cycles at 5 C with an average decay of only 0.027 % per cycle. This work achieved high stability of LMBs through simplified engineering.

Unveiling Intercalation Chemistry via Interference-Free Characterization Toward Advanced Aqueous Zinc/Vanadium Pentoxide Batteries.

Aqueous Zn/V2O5 batteries are featured for high safety, low cost, and environmental compatibility. However, complex electrode components in real batteries impede the fundamental understanding of phase transition processes and intercalation chemistry. Here, model batteries based on V2O5 film electrodes which show similar electrochemical behaviors as the real ones are built. Advanced surface science characterizations of the film electrodes allow to identify intercalation trajectories of Zn2+, H2O, and H+ during V2O5 phase transition processes. Protons serve as the vanguard of intercalated species, facilitating the subsequent intercalation of Zn2+ and H2O. The increase of capacity in the activation process is mainly due to the transition from V2O5 to more active V2O5·nH2O structure caused by the partial irreversible deintercalation of H2O rather than the increase of active sites induced by the grain refinement of electrode materials. Eventually, accumulation of Zn species within the oxide electrode results in the formation of inactive (Zn3(OH)2V2O7·2H2O) structure. The established intercalation chemistry helps to design high-performance electrode materials.

The centromere landscapes of four karyotypically diverse Papaver species provide insights into chromosome evolution and speciation.

Understanding the roles played by centromeres in chromosome evolution and speciation is complicated by the fact that centromeres comprise large arrays of tandemly repeated satellite DNA, which hinders high-quality assembly. Here, we used long-read sequencing to generate nearly complete genome assemblies for four karyotypically diverse Papaver species, P. setigerum (2n = 44), P. somniferum (2n = 22), P. rhoeas (2n = 14), and P. bracteatum (2n = 14), collectively representing 45 gapless centromeres. We identified four centromere satellite (cenSat) families and experimentally validated two representatives. For the two allopolyploid genomes (P. somniferum and P. setigerum), we characterized the subgenomic distribution of each satellite and identified a "homogenizing" phase of centromere evolution in the aftermath of hybridization. An interspecies comparison of the peri-centromeric regions further revealed extensive centromere-mediated chromosome rearrangements. Taking these results together, we propose a model for studying cenSat competition after hybridization and shed further light on the complex role of the centromere in speciation.

Curcumin-Encapsulated Co-ZIF-8 for Ulcerative Colitis Therapy: ROS Scavenging and Macrophage Modulation Effects.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by the disruption of the intestinal epithelial barrier. This study described the synthesis and characterization of CCM-Co-ZIF-8, a novel composite material with enzyme-like activities similar to catalase, peroxidase, and superoxide dismutase. CCM-Co-ZIF-8 demonstrated the ability to scavenge reactive oxygen species that play a critical role in UC pathogenesis. In vitro studies using lipopolysaccharide-induced RAW264.7 cells showed that CCM-Co-ZIF-8 exhibited anti-inflammatory activity by promoting the transition of macrophages from an M1 to an M2 phenotype. In vivo experiments using a mouse model of UC demonstrated that CCM-Co-ZIF-8 suppressed the expression of proinflammatory cytokines. These findings suggested that CCM-Co-ZIF-8 might hold promise as a therapeutic strategy for the treatment of UC.

Dilemmas in Elderly Diabetes and Clinical Practice Involving Traditional Chinese Medicine.

Diabetes is a widespread chronic disease that occurs mainly in the elderly population. Due to the difference in pathophysiology between elderly and young patients, the current clinical practice to treat elderly patients with anti-diabetes medications still faces some challenges and dilemmas, such as the urgent need for early diagnosis and prevention, and an imbalance between restricted dietary intake and the risk of undernutrition. Traditional Chinese medicine (TCM) offers various treatment regimens that are actively utilized in the field of diabetes management. Through multiple targets and multiple pathways, TCM formulas, medicinal herbs, and active natural products enhance the efficacy of diabetes prevention and diabetes control measures, simplify complex medication management, and improve common symptoms and common diabetic complications in elderly people. Historically, natural products have played a key role in material composition analysis of TCM and mechanism interpretation to enable drug discovery. However, there have been few conclusions on this topic. This review summarizes the development of TCM for the prevention and management of diabetes in elderly people, existing evidence-based clinical practices, and prospects for future development.

Multi-Source Feature-Fusion Method for the Seismic Data of Cultural Relics Based on Deep Learning.

The museum system is exposed to a high risk of seismic hazards. However, it is difficult to carry out seismic hazard prevention to protect cultural relics in collections due to the lack of real data and diverse types of seismic hazards. To address this problem, we developed a deep-learning-based multi-source feature-fusion method to assess the data on seismic damage caused by collected cultural relics. Firstly, a multi-source data-processing strategy was developed according to the needs of seismic impact analysis of the cultural relics in the collection, and a seismic event-ontology model of cultural relics was constructed. Additionally, a seismic damage data-classification acquisition method and empirical calculation model were designed. Secondly, we proposed a deep learning-based multi-source feature-fusion matching method for cultural relics. By constructing a damage state assessment model of cultural relics using superpixel map convolutional fusion and an automatic data-matching model, the quality and processing efficiency of seismic damage data of the cultural relics in the collection were improved. Finally, we formed a dataset oriented to the seismic damage risk analysis of the cultural relics in the collection. The experimental results show that the accuracy of this method reaches 93.6%, and the accuracy of cultural relics label matching is as high as 82.6% compared with many kinds of earthquake damage state assessment models. This method can provide more accurate and efficient data support, along with a scientific basis for subsequent research on the impact analysis of seismic damage to cultural relics in collections.

Transcendent thinking counteracts longitudinal effects of mid-adolescent exposure to community violence in the anterior cingulate cortex.

Adolescence involves extensive brain maturation, characterized by social sensitivity and emotional lability, that co-occurs with increased independence. Mid-adolescence is also a hallmark developmental stage when youths become motivated to reflect on the broader personal, ethical, and systems-level implications of happenings, a process we term transcendent thinking. Here, we examine the confluence of these developmental processes to ask, from a transdisciplinary perspective, how might community violence exposure (CVE) impact brain development during mid-adolescence, and how might youths' dispositions for transcendent thinking be protective? Fifty-five low-SES urban youth with no history of delinquency (32 female; 27 Latinx, 28 East Asian) reported their CVE and underwent structural MRI first at age 14-18, and again 2 years later. At the study's start, participants also discussed their feelings about 40 minidocumentaries featuring other teens' compelling situations in a 2-h private interview that was transcribed and coded for transcendent thinking. Controlling for CVE and brain structure at the start: (1) New CVE during the 2-year inter-scan interval was associated with greater gray matter volume (GMV) reduction over that interval in the anterior cingulate cortex (ACC), a central network hub whose reduced volume has been associated with posttraumatic stress disorder, and across multiple additional cortical and subcortical regions; (2) participants' transcendent thinking in the interview independently predicted greater GMV increase during the 2-year inter-scan interval in the ACC. Findings highlight the continued vulnerability of mid-adolescents to community violence and the importance of supporting teens' dispositions to reflect on the complex personal and systems-level implications and affordances of their civic landscape.

N-Containing Porous Carbon-Based MnO Composites as Anode with High Capacity and Stability for Lithium-Ion Batteries.

MnO has attracted much attention as the anode for Li-ion batteries (LIBs) owing to its high specific capacity. However, the low conductivity limited its large application. An effective solution to solve this problem is carbon coating. Biomass carbon materials have aroused much interest for being low-cost and rich in functional groups and hetero atoms. This work designs porous N-containing MnO composites based on the chemical-activated tremella using a self-templated method. The tremella, after activation, could offer more active sites for carbon to coordinate with the Mn ions. And the as-prepared composites could also inherit the special porous nanostructures of the tremella, which is beneficial for Li+ transfer. Moreover, the pyrrolic/pyridinic N from the tremella can further improve the conductivity and the electrolyte wettability of the composites. Finally, the composites show a high reversible specific capacity of 1000 mAh g-1 with 98% capacity retention after 200 cycles at 100 mA g-1. They also displayed excellent long-cycle performance with 99% capacity retention (relative to the capacity second cycle) after long 1000 cycles under high current density, which is higher than in most reported transition metal oxide anodes. Above all, this study put forward an efficient and convenient strategy based on the low-cost biomass to construct N-containing porous composite anodes with a fast Li+ diffusion rate, high electronic conductivity, and outstanding structure stability.

Pindel-TD: A Tandem Duplication Detector Based on A Pattern Growth Approach.

Tandem duplication (TD) is a major type of structural variations (SVs) that plays an important role in novel gene formation and human diseases. However, TDs are often missed or incorrectly classified as insertions by most modern SV detection methods due to the lack of specialized operation on TD-related mutational signals. Herein, we developed a TD detection module for the Pindel tool, referred to as Pindel-TD, based on a TD-specific pattern growth approach. Pindel-TD is capable of detecting TDs with a wide size range at single nucleotide resolution. Using simulated and real read data from HG002, we demonstrated that Pindel-TD outperforms other leading methods in terms of precision, recall, F1-score, and robustness. Furthermore, by applying Pindel-TD to data generated from the K562 cancer cell line, we identified a TD located at the seventh exon of SAGE1, providing an explanation for its high expression. Pindel-TD is available for non-commercial use at https://github.com/xjtu-omics/pindel.

Fabrication of photo-induced molecular superoxide radical generator for highly efficient therapy against bacterial wound infection.

The pressing need for highly efficient antibacterial strategies arises from the prevalence of microbial biofilm infections and the emergence of rapidly evolving antibiotic-resistant strains of pathogenic bacteria. Photodynamic therapy represents a highly efficient and compelling antibacterial approach, offering promising prospects for effective control of the development of bacterial resistance. However, the effectiveness of many photosensitizers is limited due to the reduced generation of reactive oxygen species (ROS) in hypoxic microenvironment, which commonly occur in pathological conditions such as inflammatory and bacteria-infected wounds. Herein, we designed and prepared two phenothiazine-derived photosensitizers (NB-1 and NB-2), which can effectively generate superoxide anion radicals (O2●-) through the type I process. Both photosensitizers demonstrate significant efficacy in vitro for the eradication of broad-spectrum bacteria. Moreover, NB-2 possesses distinct advantages including strong membrane binding and strong generation of O2●-, rendering it an exceptionally efficient antibacterial agent against mature biofilms. In addition, laser activated NB-2 could be applied to treat MRSA-infected wound in vivo, which offers new opportunities for potential practical applications.

Design and prediction of laser-induced damage threshold of CNT-PDMS optoacoustic transducer.

The optoacoustic transducer has emerged as a new candidate for medical ultrasound applications and attracts considerable attention. Optoacoustic diagnosis and treatment sometimes require high-intensity acoustic pressure, which is often accompanied by the problem of laser-induced damage. Addressing the laser-induced damage phenomenon from a theoretical perspective holds paramount importance. In this study, the theoretical model of laser-induced damage of the carbon nanotubes-polydimethylsiloxane (CNT-PDMS) composite optoacoustic transducer is established. It is found that this laser-induced damage belongs to thermal ablation damage. Furthermore, the correctness of this theory can be confirmed by experimental results. Most importantly, when the laser energy density is less than threshold value of laser energy density, the optoacoustic transducer can work stable for long time. These encouraging results demonstrate that this work can provide significant guidance for the exploration and utilization of optoacoustic transducers.

Using ultrasonic washing combined with UV-LEDs as a novel chemical-free method to disinfect fresh ready-to-eat produce.

The consumption of ready-to-eat fresh produce raises the issue of food-borne pathogen infections; thus, disinfecting ready-to-eat produce for commercial use, such as in homes and restaurants, is important to ensure food safety. Chemical sanitizers are typically used for disinfection. Ultraviolet-light emitting diodes (UV-LEDs) are a novel non-thermal disinfection technology that consumes less energy and generates less heat than traditional UV lamps, making them more appealing to consumers. In this study, we combined ultrasonic (US) washing method with UV-LEDs (US-UV-LEDs) to develop a technique for disinfecting fresh produce without using chemical sanitizers and compared its efficacy with three common household sanitizers ("84" (sodium hypochlorite) disinfectant, kettle descaler (citric acid), and vinegar (acetic acid)). In addition, we investigated the efficacy of this method in controlling pathogen numbers in the water used to wash (washing water) the produce to prevent cross-contamination between water and produce. Cherry tomatoes and lettuce were selected as produce models and Salmonella Typhimurium and Escherichia coli O157:H7 were used as the bacterial models. The results showed that US-UV-LEDs reduced the numbers of S. Typhimurium and E. coli O157:H7 on produce by 2.1-2.2 log CFU/g, consistent with the results achieved by the three household sanitizers; however, kettle descaler and vinegar had a limited effect (2.6-3.5 log CFU/mL) on residual pathogens in the washing water. Furthermore, we created washing water with low (754 mg/L) and high (1425 mg/L) chemical oxygen demand (COD) levels and determined the disinfection efficacy of "84" disinfectant and US-UV-LEDs. The results showed that US-UV-LEDs reduced the number of S. Typhimurium and E. coli O157:H7 by 2.0-2.1 and 1.8-2.1 log CFU/g under low and high COD levels, respectively, which was similar a result to that of "84" disinfectant. However, the residual pathogen numbers in the washing water were reduced to 1.4-1.9 log CFU/mL after treatment with US-UV-LED under high COD, whereas the pathogens were undetected in the washing water disinfected with "84" disinfectant. These results suggest that US-UV-LEDs have better application potential than acidic household sanitizers, but chlorine sanitizer remains the most effective disinfecting method.

Ct-defined emphysema prevalence in a Chinese and Dutch general population.

PURPOSE: We determine and compare the prevalence, subtypes, severity, and risk factors for emphysema assessed by low-dose CT(LDCT) in Chinese and Dutch general populations. METHODS: This cross-sectional study included LDCT scans of 1143 participants between May and October 2017 from a Chinese Cohort study and 1200 participants with same age range and different smoking status between May and October 2019 from a Dutch population-based study. An experienced radiologist visually assessed the scans for emphysema presence (≥trace), subtype, and severity. Logistic regression analyses, overall and stratified by smoking status, were performed and adjusted for fume exposure, demographic and smoking data. RESULTS: The Chinese population had a comparable proportion of women to the Dutch population (54.9 % vs 58.9 %), was older (61.7 ± 6.3 vs 59.8 ± 8.1), included more never smokers (66.4 % vs 38.3 %), had a higher emphysema prevalence ([58.8 % vs 39.7 %], adjusted odds ratio, aOR = 2.06, 95 %CI = 1.68-2.53), and more often had centrilobular emphysema (54.8 % vs 32.8 %, p < 0.001), but no differences in emphysema severity. After stratification, only in never smokers an increased odds of emphysema was observed in the Chinese compared to the Dutch (aOR = 2.55, 95 %CI = 1.95-3.35). Never smokers in both populations shared older age (aOR = 1.59, 95 %CI = 1.25-2.02 vs 1.26, 95 %CI = 0.97-1.64) and male sex (aOR = 1.50, 95 %CI = 1.02-2.22 vs 1.93, 95 %CI = 1.26-2.96) as risk factors for emphysema. CONCLUSIONS: Only never smokers had a higher prevalence of mainly centrilobular emphysema in the Chinese general population compared to the Dutch after adjusting for confounders, indicating that factors other than smoking, age and sex contribute to presence of CT-defined emphysema.

Effect of emphysema on AI software and human reader performance in lung nodule detection from low-dose chest CT.

BACKGROUND: Emphysema influences the appearance of lung tissue in computed tomography (CT). We evaluated whether this affects lung nodule detection by artificial intelligence (AI) and human readers (HR). METHODS: Individuals were selected from the "Lifelines" cohort who had undergone low-dose chest CT. Nodules in individuals without emphysema were matched to similar-sized nodules in individuals with at least moderate emphysema. AI results for nodular findings of 30-100 mm3 and 101-300 mm3 were compared to those of HR; two expert radiologists blindly reviewed discrepancies. Sensitivity and false positives (FPs)/scan were compared for emphysema and non-emphysema groups. RESULTS: Thirty-nine participants with and 82 without emphysema were included (n = 121, aged 61 ± 8 years (mean ± standard deviation), 58/121 males (47.9%)). AI and HR detected 196 and 206 nodular findings, respectively, yielding 109 concordant nodules and 184 discrepancies, including 118 true nodules. For AI, sensitivity was 0.68 (95% confidence interval 0.57-0.77) in emphysema versus 0.71 (0.62-0.78) in non-emphysema, with FPs/scan 0.51 and 0.22, respectively (p = 0.028). For HR, sensitivity was 0.76 (0.65-0.84) and 0.80 (0.72-0.86), with FPs/scan of 0.15 and 0.27 (p = 0.230). Overall sensitivity was slightly higher for HR than for AI, but this difference disappeared after the exclusion of benign lymph nodes. FPs/scan were higher for AI in emphysema than in non-emphysema (p = 0.028), while FPs/scan for HR were higher than AI for 30-100 mm3 nodules in non-emphysema (p = 0.009). CONCLUSIONS: AI resulted in more FPs/scan in emphysema compared to non-emphysema, a difference not observed for HR. RELEVANCE STATEMENT: In the creation of a benchmark dataset to validate AI software for lung nodule detection, the inclusion of emphysema cases is important due to the additional number of FPs. KEY POINTS: • The sensitivity of nodule detection by AI was similar in emphysema and non-emphysema. • AI had more FPs/scan in emphysema compared to non-emphysema. • Sensitivity and FPs/scan by the human reader were comparable for emphysema and non-emphysema. • Emphysema and non-emphysema representation in benchmark dataset is important for validating AI.

Novel Dual-Emission Emitters Featuring Phenothiazine-S-Oxide and Phenothiazine-S,S-Dioxide Motifs.

In this study, we have successfully designed and synthesized two novel dual-emission emitters featuring phenothiazine-5-oxide and phenothiazine-5,5-dioxide motifs, characterized by highly lopsided and asymmetric conformational states. Through rigorous spectral examinations and DFT calculations, the compounds exhibit distinctive ICT phenomena, coupled with efficient emission in solid states and AIEE characteristics under high water fractions in DMF/H2O mixtures. These non-planar luminogens exhibit vibrant green and blue solid-state luminescence, with fluorescence quantum yields of 24.1 % and 15.21 %, respectively. Additionally, they both emit green fluorescence in THF solution, with notable emission quantum yields (QYs) 36.4 % and 30.4 %. Comprehensive theoretical investigations unveil well-defined electron cloud density separation between the energies of HOMO/LUMO levels within the two luminogens. Notably, the targeted molecule harboring the phenothiazine-S,S-dioxide motif also demonstrates remarkable reversible mechanofluorochromic properties. Moreover, we testify their potential in applications such as solid-state rewritable information storage and live-cell imaging in solution states. Through theoretical calculations and comparative studies, we have explored the intrinsic relationship between molecular structure and performance, effectively screening and identifying new fluorescent molecules exhibiting outstanding luminescent attributes. These discoveries establish a robust theoretical and technical foundation for the synthesis and application of efficient DSE-based MFC materials, opening new avenues in the realm of advanced luminescent materials.